¹H NMR Studies of Glucose Transport in the Human Brain

Abstract

The difference between 1H nuclear magnetic resonance (NMR) spectra obtained from the human brain during euglycemia and during hyperglycemia is depicted as well-resolved glucose peaks. The time course of these brain glucose changes during a rapid increase in plasma glucose was measured in four healthy subjects, aged 18-22 years, in five studies. Results demonstrated a significant lag in the rise of glucose with respect to plasma glucose. The fit of the integrated symmetric Michaelis-Menten model to the time course of relative glucose signals yielded an estimated plasma glucose concentration for half maximal transport, Kt, of 4.8 +/- 2.4 mM (mean +/- SD), a maximal transport rate, Tmax, of 0.80 +/- 0.45 micromol g-1 min-1, and a cerebral metabolic glucose consumption rate (CMR)glc of 0.32 +/- 0.16 micromol g-1 min-1. Assuming cerebral glucose concentration to be 1.0 micromol/g at euglycemia as measured by 13CMR, the fit of the same model to the time course of brain glucose concentrations resulted in Kt = 3.9 +/- 0.82 mM, Tmax = 1.16 +/- 0.29 micromol g-1 min-1, and CMRglc = 0.35 +/- 0.10 micromol g-1 min-1. In both cases, the resulting time course equaled that predicted from the determination of the steady-state glucose concentration by 13C NMR spectroscopy within the experimental scatter. The agreement between the two methods of determining transport kinetics suggests that glucose is distributed throughout the entire aqueous phase of the human brain, implying substantial intracellular concentration.

Differentiation of Glucose Transport in Human Brain Gray and White Matter

“…This assumption is supported by isolated cell studies that have shown high glucose transport activity on neurons and glia (Lund-Andersen 1979;Vannucci et al, 1997). The in vivo magnetic resonance spectroscopy study of Gruetter et al (1996) found a significantly slower time course in the increase of brain glucose relative to plasma glucose during a rapid glucose infusion, which agreed with the kinetics predicted for uniform glucose distribution between brain compartments. We found a similar lag in brain glucose concentration.…”

“…When the effects of hexokinase are ignored (K m Ј ‫ס‬ 0), Eq. 4 reduces to the well-known, asymptotic relationship previously described (Gruetter et al 1996Lund-Andersen, 1979).…”

Simultaneous Measurement of Glucose Blood–Brain Transport Constants and Metabolic Rate in Rat Brain using in-vivo1H MRS

“…It is clear that the observed signal increases of multiple 1 H NMR resonance peaks (chemical shifts 3.0 to 5.2 p.p.m.) after glucose infusion come from a brain glucose concentration change, which has been observed in previous human or animal brain glucose infusion studies (Gruetter et al, 1992(Gruetter et al, , 1996(Gruetter et al, , 1998. The rat brain glucose resonance peak at B5.2 p.p.m.…”

Studies of metabolic compartmentation and glucose transport using in vivo MRS

“…5 Glutamine is released from the glia to the ECF where it is taken up by neurons and converted back to glutamate through the action of phosphate activated glutaminase (PAG). 6 Based on extensive data from isotopic labeling studies, immunohistochemical staining of cortical cells for specific enzymes, isolated cells and tissue fractionation studies it has been proposed that 66 GABAergic neurons Energy metabolism Inhibitory neurotransmission Glucose 47,50 Neurons/glia Glucose transport Glutamine 13,42 Glia Glutamate neurotransmitter cycling Ammonia detoxification Osmotic regulation Glial pH Homocarnosine 67 Subclass of GABAergic neurons pH, inhibitory neuromodulation NAA 68 Neurons Volume Mitochondrial function Myoinositol 69 Glia Osmotic regulation glutamate (as well as GABA) taken up by the glia from the synaptic cleft may be returned to the neuron in the form of glutamine. [7][8][9][10] Figure 1 shows the currently accepted model of the glutamine/glutamate cycle.…”